1. Field of the Invention
Coronary artery disease continues to be a leading cause of death in most developed countries in the world. Although a number of prophylactic measures can reduce mortality in individuals suffering from coronary artery disease, such as dietary modification and exercise programs, it is necessary to identify those individuals who are at risk or suffering from such coronary artery disease to take advantage of these measures.
Recently, screening techniques which rely on the presence of abnormal lipoprotein serum profiles to identify individuals at risk have been developed. Such techniques, however, have not been entirely satisfactory. Extreme variability in the amount of serum lipoproteins among individuals will obscure the small differences between normal and coronary-prone patients. While absolute levels or ratios of low density lipoprotein (LDL), high density lipoprotein (HDL) and HDL-associated and LDL-associated cholesterol generally correlate with cardiovascular mortality based on average levels in the population as a whole, quantitative differences among individuals are small, standard errors are large, and the predictive value of such tests remain unproven.
It would thus be desirable to provide a reliable, rapid, and efficient technique for screening large numbers of individuals to determine individuals who are suffering from or at risk from a coronary artery disease.
2. Description of the Prior Art
Krauss et al. (1980) Clin. Chim. Acta. 104:275-290 report that serum levels of smaller slower floating low density lipoprotein (LDL) subspecies (S.sub.f &lt;7) correlate inversely with levels of high density lipoprotein (HDL). Shen et al. (1981) J. Lipid Res. 22:236-244 and Lindgren et al. (1981) in: "AOCS Conference on Dietary Fats and Health", Perkins and Visek, eds., Chicago 1981, describe the separation of six subfractions of LDL from normal subjects by equilibrium density gradient ultracentrifugation. Krauss and Burke (1982) J. Lipid Res. 23:97-104 report that discrete subpopulations of LDL in normal subjects can be differentiated on the basis of characteristic hydrated densities and particle sizes. Maciejko et al. (1983) N. Eng. J. Med. 309:385-389 describe the identification of apolipoprotein A-I as a marker for patients suffering from coronary-artery disease. Blackburn (1983) N. Eng. J. Med. 309:426-428, provides a critical discussion of the report of Maciejko et al. Monoclonal antibodies raised against LDL's, including apolipoprotein B, have been reported. See, e.g., Tikkanen et al. ( 1982) J. Lipid Res. 23:1032-1038; Marcel et al. (1982) J. Biol. Chem. 257:13165-13168; Mao et al. (1982) Biochem. Biophys. Acta 713:365-374; Curtiss and Edgington (1982) J. Biol. Chem. 257:15213-15221; and Tsao et al. (1982) J. Biol. Chem. 257:15222-15228.